In the Cholesterol Lowering Atherosclerosis Study, Blankenhorn, Malinow et al. reported an increase in plasma homocyst(e)ine levels in patients on both colestipol and niacin compared to placebo. Thus, the objective was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The arterial Disease Multiple Intervention Trial was a multi-center, randomized, placebo-controlled trial of participants with peripheral arterial disease who were randomized to niacin or placebo. A subset of 52 participants with plasma homocyst(e)ine levels were examined for the relationship between niacin and plasma homocyst(e)ine levels. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine levels from 13.4 ? 4.4 umol/L to 15.3 ? 5.6 umol/l (p<0.0001). At 18 weeks post-randomization, there was an absolute 55% increase from baseline in mean plasma homocyst(e)ine levels for the group assigned to 3000 mg of niacin daily and a 7% decrease in the placebo group (p=0.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels. This could potentially reduce the expected benefits of niacin associated with lipoprotein modification. Thus, studies are needed to determine whether vitamin supplementation to patients on long-term niacin treatment would be beneficial. FUNDING Collaboration with University of Minnesota PUBLICATIONS None